10.1021/jo4024705
The research explores a method for synthesizing CF2-containing compounds from three components: organozinc reagents, difluorocarbene, and allylic electrophiles. The purpose is to develop a more efficient and mild synthetic route for creating organofluorine compounds, which are of increasing interest in medicinal chemistry due to the CF2 fragment's ability to act as a bioisoster of ether oxygen and a carbonyl group. The study concludes that the reaction, involving the insertion of difluorocarbene into the carbon-zinc bond followed by copper-catalyzed allylic substitution, successfully forms two C-C bonds in one step under mild conditions. Key chemicals used include (Bromodifluoromethyl)trimethylsilane as a source of difluorocarbene, various organozinc reagents like methoxycarbonylbenzylzinc bromide, and allylic electrophiles such as allyl bromide and allyl chloride. The presence of copper (I) salts, specifically copper iodide, was crucial for inducing the zinc/copper exchange and facilitating the coupling reaction. The method demonstrated good tolerance for functional groups like esters and nitriles and provided products in good yields, highlighting its potential for practical applications in synthesizing complex fluorinated molecules.
10.1016/j.tetlet.2013.07.029
The study presents a copper-catalyzed one-pot synthesis of alkynyl imidates and alkynyl thioimidates through a coupling reaction involving terminal alkynes, trichloroimidates generated in situ from trichloroacetonitrile and benzyl alcohols or thiols. The key chemicals include phenylacetylene as a model terminal alkyne, trichloroacetonitrile as a precursor for trichloroimidates, and benzyl alcohol or thiol as the source of the imidate or thioimidate group. Copper iodide (CuI) acts as the catalyst, and triethylamine (Et3N) is used as a base. The reaction is optimized in acetonitrile at room temperature, yielding the desired products in good yields. The mechanism involves the formation of a copper acetylide intermediate, which reacts with the trichloroimidates to form a tetrahedral intermediate, followed by the elimination of CuCCl3 to produce the final products. This method offers a versatile and efficient route for synthesizing functionalized alkynes with readily available starting materials and catalysts.
